Genetically Determined Reproductive Aging and Coronary Heart Disease: A Bidirectional 2-sample Mendelian Randomization

被引：16

作者：

Dam, Veerle ^{[1
,2
]}

Onland-Moret, N. Charlotte ^{[1
]}

Burgess, Stephen ^{[3
,4
,5
]}

Chirlaque, Maria-Dolores ^{[6
,7
]}

Peters, Sanne A. E. ^{[1
,8
]}

Schuit, Ewoud ^{[1
]}

Tikk, Kaja ^{[9
,10
]}

Weiderpass, Elisabete ^{[11
]}

Oliver-Williams, Clare ^{[4
,5
]}

Wood, Angela M. ^{[4
]}

Tjonneland, Anne ^{[12
,13
]}

Dahm, Christina C. ^{[14
]}

Overvad, Kim ^{[14
,15
]}

Boutron-Ruault, Marie-Christine ^{[16
,17
]}

Schulze, Matthias B. ^{[18
]}

Trichopoulou, Antonia ^{[19
,20
]}

Ferrari, Pietro ^{[11
]}

Masala, Giovanna ^{[21
]}

Krogh, Vittorio ^{[22
]}

Tumino, Rosario ^{[23
]}

Matullo, Giuseppe ^{[24
,25
]}

Panico, Salvatore ^{[26
]}

Boer, Jolanda M. A. ^{[27
]}

Verschuren, W. M. Monique ^{[1
,27
]}

Waaseth, Marit ^{[28
]}

Sanchez Perez, Maria Jose ^{[29
,30
]}

Amiano, Pilar ^{[30
,31
]}

Imaz, Liher ^{[30
,31
]}

Moreno-Iribas, Conchi ^{[32
]}

Melander, Olle ^{[33
]}

Harlid, Sophia ^{[34
]}

Nordendahl, Maria ^{[7
]}

Wennberg, Patrik ^{[7
]}

Key, Timothy J. ^{[35
]}

Riboli, Elio ^{[36
]}

Santiuste, Carmen ^{[30
,37
]}

Kaaks, Rudolf ^{[38
]}

Katzke, Verena ^{[38
]}

Langenberg, Claudia ^{[39
]}

Wareham, Nicholas J. ^{[39
]}

Schunkert, Heribert ^{[40
,41
]}

Erdmann, Jeanette ^{[42
]}

Willenborg, Christina ^{[42
]}

Hengstenberg, Christian ^{[43
]}

Kleber, Marcus E. ^{[44
]}

Delgado, Graciela ^{[44
]}

Marz, Winfried ^{[44
,45
,46
]}

Kanoni, Stavroula ^{[47
]}

Dedoussis, George ^{[48
]}

Deloukas, Panos ^{[47
,49
,50
]}

机构：

[1] Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-3508 GA Utrecht, Netherlands

[2] Netherlands Heart Inst, NL-3501 DG Utrecht, Netherlands

[3] Univ Cambridge, MRC Biostat Unit, Cambridge CB2 0SR, England

[4] Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England

[5] Homerton Coll, Cambridge, England

[6] Murcia Univ, Dept Epidemiol, IMIB Arrixaca, Reg Hlth Author, Murcia 30001, Spain

[7] Imperial Coll London, George Inst Global Hlth, London W12 0BZ, England

[8] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany

[9] DKFZ, German Canc Consortium, D-69120 Heidelberg, Germany

[10] World Hlth Org, Int Agcy Res Canc, F-69372 Lyon, France

[11] Danish Canc Soc Res Ctr, DK-2100 Copenhagen, Denmark

[12] Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, DK-2200 Copenhagen, Denmark

[13] Aarhus Univ, Dept Publ Hlth, DK-8000 Aarhus, Denmark

[14] Aalborg Univ Hosp, Dept Cardiol, DK-9000 Aalborg, Denmark

[15] Inst Gustave Roussy, Ctr Res Epidemiol & Populat Hlth, Nutr Hormones & Womens Hlth Team, U1018,INSERM, Villejuif, France

[16] German Inst Human Nutr, Dept Epidemiol, Potsdam, Nuthetal, Germany

[17] Univ Potsdam, Inst Nutr Sci, D-14558 Nuthetal, Germany

[18] Hellen Hlth Fdn, Athens, Greece

[19] Natl & Kapodistrian Univ Athens, WHO Collaborating Ctr Nutr & Hlth, Sch Med,Unit Nutr Epidemiol & Nutr Publ Hlth, Dept Hyg Epidemiol & Med Stat, Athens 11527, Greece

[20] Inst Canc Res Prevent & Clin Network ISPRO, Canc Risk Factors & Life Style Epidemiol Unit, I-50139 Florence, Italy

[21] Fdn IRCCS Ist Nazl Tumori, Epidemiol & Prevent Unit, I-20133 Milan, Italy

[22] ASP Ragusa, Canc Registry & Histopathol Dept, Civ MP Arezzo hosp, I-97100 Ragusa, Italy

[23] Univ Torino, Dept Med Sci, I-10124 Turin, Italy

[24] Italian Inst Genom Med IIGM HuGeF, I-10126 Turin, Italy

[25] Univ Naples Federico II, Dipartimento Med Clin & Chirurg, I-80126 Naples, Italy

[26] Natl Inst Publ Hlth & Environm RIVM, NL-3720 BA Bilthoven, Netherlands

[27] UiT Arctic Univ Norway, Fac Hlth Sci, Dept Pharm, N-9037 Tromso, Norway

[28] Univ Granada, Escuela Andaluza Salud Publ, Inst Invest Biosanitaria Ibs GRANADA, Granada 18011, Spain

[29] CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain

[30] Biodonostia Res Inst, Publ Hlth Div Gipuzkoa, San Sebastian 20014, Spain

[31] REDISSEC, Navarre Inst Hlth Res, Inst Salud Publ Navarra, IdiSNA, Pamplona 31008, Spain

[32] Lund Univ, Dept Clin Sci, SE-22100 Malmo, Sweden

[33] Umea Univ, Dept Radiat Sci, Oncol, S-90187 Umea, Sweden

[34] Umea Univ, Dept Publ Hlth & Clin Med, S-90187 Umea, Sweden

[35] Univ Oxford, Nuffield Dept Populat Hlth, Oxford OX3 7LF, England

[36] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London SW7 2AZ, England

[37] IMIB Arrixaca, Dept Epidemiol, Murcia Reg Hlth Author, Murcia 30001, Spain

[38] Fdn Publ Law, German Canc Res Ctr, Div Canc Epidemiol, DKFZ, D-69120 Heidelberg, Germany

[39] Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Cambridge CB2 0SL, England

[40] Tech Univ Munich, Deutsch Herzzentrum Munchen, D-80636 Munich, Germany

[41] DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Allicance, D-80636 Munich, Germany

[42] Univ Lubeck, Inst Cardiogenet, D-23562 Lubeck, Germany

[43] Med Univ Vienna, Dept Internal Med 2, Div Cardiol, A-1090 Vienna, Austria

[44] Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany

[45] Synlab Holding Deutschland GmbH, Synlab Acad, D-68167 Mannheim, Germany

[46] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, A-8036 Graz, Austria

[47] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London E1 4NS, England

[48] Harokopio Univ, Dept Nutr Dietet, Athens 17671, Greece

[49] Queen Mary Univ London, Ctr Genom Hlth, London E1 4NS, England

[50] King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21589, Saudi Arabia

来源：

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM | 2022年 / 107卷 / 07期

基金：

欧洲研究理事会; 英国惠康基金; 英国医学研究理事会;

关键词：

reproductive aging; Mendelian Randomization; coronary heart disease; risk factors; GENOME-WIDE ASSOCIATION; FASTING GLUCOSE; MENOPAUSE; RISK; AGE; VARIANTS; IMPACT; MORTALITY; BIAS;

D O I：

10.1210/clinem/dgac171

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Accelerated reproductive aging, in women indicated by early natural menopause, is associated with increased coronary heart disease (CHD) risk in observational studies. Conversely, an adverse CHD risk profile has been suggested to accelerate menopause. Objectives To study the direction and evidence for causality of the relationship between reproductive aging and (non-)fatal CHD and CHD risk factors in a bidirectional Mendelian randomization (MR) approach, using age at natural menopause (ANM) genetic variants as a measure for genetically determined reproductive aging in women. We also studied the association of these variants with CHD risk (factors) in men. Design Two-sample MR, using both cohort data as well as summary statistics, with 4 methods: simple and weighted median-based, standard inverse-variance weighted (IVW) regression, and MR-Egger regression. Participants Data from EPIC-CVD and summary statistics from UK Biobank and publicly available genome-wide association studies were pooled for the different analyses. Main Outcome Measures CHD, CHD risk factors, and ANM. Results Across different methods of MR, no association was found between genetically determined reproductive aging and CHD risk in women (relative risk estimate(IVW) = 0.99; 95% confidence interval (CI), 0.97-1.01), or any of the CHD risk factors. Similarly, no associations were found in men. Neither did the reversed analyses show evidence for an association between CHD (risk factors) and reproductive aging. Conclusion Genetically determined reproductive aging is not causally associated with CHD risk (factors) in women, nor were the genetic variants associated in men. We found no evidence for a reverse association in a combined sample of women and men.

引用

页码：E2952 / E2961

页数：10

共 47 条

[1]

Abbott L., 2017, RAPID GWAS 1000S PHE

[2]

Aragam KG., 2021, medRxiv, DOI DOI 10.1101/2021.05.24.21257377

[3] Nonfasting Glucose, Ischemic Heart Disease, and Myocardial Infarction A Mendelian Randomization Study [J].

Benn, Marianne ;

Tybjaerg-Hansen, Anne ;

McCarthy, Mark I. ;

Jensen, Gorm B. ;

Grande, Peer ;

Nordestgaard, Borge G. .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2012, 59 (25) :2356-2365

[4] Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator [J].

Bowden, Jack ;

Smith, George Davey ;

Haycock, Philip C. ;

Burgess, Stephen .

GENETIC EPIDEMIOLOGY, 2016, 40 (04) :304-314

[5]

Burgess S., 2015, Mendelian randomization: methods for using genetic variants in causal estimation, DOI DOI 10.1201/B18084

[6] Interpreting findings from Mendelian randomization using the MR-Egger method (vol 32, pg 377, 2017) [J].

Burgess, Stephen ;

Thompson, Simon G. .

EUROPEAN JOURNAL OF EPIDEMIOLOGY, 2017, 32 (05) :391-392

[7] Bias due to participant overlap in two-sample Mendelian randomization [J].

Burgess, Stephen ;

Davies, Neil M. ;

Thompson, Simon G. .

GENETIC EPIDEMIOLOGY, 2016, 40 (07) :597-608

[8]

Collins R, 2012, LANCET, V379, P1173, DOI [10.1016/S0140-6736(12)60404-8, 10.1016/S0140-6736(16)31357-5]

[9] Causal Associations of Adiposity and Body Fat Distribution With Coronary Heart Disease, Stroke Subtypes, and Type 2 Diabetes Mellitus A Mendelian Randomization Analysis [J].

Dale, Caroline E. ;

Fatemifar, Ghazaleh ;

Palmer, Tom M. ;

White, Jon ;

Prieto-Merino, David ;

Zabaneh, Delilah ;

Engmann, Jorgen E. L. ;

Shah, Tina ;

Wong, Andrew ;

Warren, Helen R. ;

McLachlan, Stela ;

Trompet, Stella ;

Moldovan, Max ;

Morris, Richard W. ;

Sofat, Reecha ;

Kumari, Meena ;

Hypponen, Elina ;

Jefferis, Barbara J. ;

Gaunt, Tom R. ;

Ben-Shlomo, Yoav ;

Zhou, Ang ;

Gentry-Maharaj, Aleksandra ;

Ryan, Andy ;

de Mutsert, Renee ;

Noordam, Raymond ;

Caulfield, Mark J. ;

Jukema, J. Wouter ;

Worrall, Bradford B. ;

Munroe, Patricia B. ;

Menon, Usha ;

Power, Chris ;

Kuh, Diana ;

Lawlor, Debbie A. ;

Humphries, Steve E. ;

Mook-Kanamori, Dennis O. ;

Sattar, Naveed ;

Kivimaki, Mika ;

Price, Jacqueline F. ;

Smith, George Davey ;

Dudbridge, Frank ;

Hingorani, Aroon D. ;

Holmes, Michael V. ;

Casas, Juan P. .

CIRCULATION, 2017, 135 (24) :2373-+

[10]

Dam, 2022, SUPPLEMENTAL MAT, DOI 10.5281/zenodo.5638886

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